《生理学》CHAPTERIIENDOCRINESYSTE

Section3ThyroidGland 冯鉴强教授 Generalorganization thefirstendocrineglandtoberecognizedbythosesymptomsassociatedwithexcessordeficientfunction consistsoftwolobes oneoneachsideoftracheabelowcricoidscartilage 环状软骨 Lobesarecomposedofsphericalfolliclesformedbyasinglelayerofepithelialcellsthatsurroundalumenfilledwithagel likesubstancecalledcolloid 胶质 composedofthyroglobulin TG theprecursor 前体 ofthyroidhormones thyroidepithelialcellssecretethyroidhormones T4 T3 andsynthesizeTG parafollicularcellssecretecalcitonin CT 降钙素 ThyroidHormones TH THincludingthyroxin T4 3 5 3 5 triiodothyronine T3 andrT3 逆 三碘甲腺原氨酸 nobiologicalactivity Fig11 15 Synthesisandsecretionofthyroidhormones IodineisrequiredforformationofthyroxinAbout500mgofingestedarerequiredeachyear about1mg weekInternationalstandard 150 g dTopreventiodinedeficiency saltisiodizedwithsodiumiodide iodide NaCl 1 100 000 Absorbedfromgastrointestinaltractinthesamemanneraschloride SynthesisandsecretionofTHinclude4stages 1 IodideTrapping 碘捕获 Uptakeofiodideions I fromthebloodbyepithelialcellsofthefollicleviaanactivetransportsystemthatco transportsNa ionsintothecell transportofiodineincluding2steps atbasalmembrane transportedactivelyintocellagainstelectrical chemicalgradientbyasodium iodidesymportor 钠 碘同向转运体 也称Na I 泵 I concentrationinsidethyroidglandis20 25timesthaninthebloodTherestingmembranepotentialofepitheliacellisabout 40 50mV Na I pumprequiresenergyprovidedbyNa K ATPaseATP Na K ATPaseactivity extracellularNa Na diffuseinside I transportedbyNa I pump Iiodine 2Na contransport 协同转运 Someions ClO4 SCN NO3 tocompeteagainstI transport TSH tostimulateandhypophysectomygreatlydiminishestheactivityofiodidepump Ibeusedtotestabilityofiodidetrappingandfunctionofthyroidgland 2 Iodideoxidationandiodinationtyrosine Iodide I isoxidizedtoiodine I bythyroidperoxidase TPO 甲状腺过氧化物酶 TPOeitherlocatedintheapicalmembraneofthecellorattachedtoitTPOisblocked therateofformationofTHfallstozero Theoxidizediodinebindswithtyrosineresidues 残基 ofTG ThisprocessiscallediodinationoftyrosisTyrosineisfirstiodizedtoformmonoiodotyrosine MIT 一碘甲腺原氨酸 thentodiiodotyrosine DIT 二碘甲腺原氨酸 3 Condensationoftheiodotyrosine 碘化酪氨酸得缩合 MIT DIT TPO T3DIT DIT TPO T4DIT MIT TPO rT3 PercentageofthyroidhormonesMIT23 DIT33 T37 T435 rT3andotherelements2 StorageofthyroidhormonesIodinatedthyroglobulinstoredinthelumenaspartofthecolloid1moleculeofTGcontains6moleculesMIT 5DIT upto30T4andafewT3 Fig11 16 4 Releaseofthyroidhormonehormones toformpinocytoticvesicle 吞饮小泡 lysosomesfusewiththesevesiclestoformdigestivevescles multipleproteinasesdigesttheTGandreleaseT4 T3 DITandMIT MITandDIT deiodinase I andtyrosine recyclingforformationofTHCongenitalabsenceofiodotyrosinedeiodinase 碘化酪氨酸脱碘酶 leadstoiodine deficiencyDailyrateofsecretionofT4andT3T480 g day T34 g dayAmongTH 93 isT4 7 T3AboutonehalfofT4 T3 TransportanddegradationofTH transporttype freestate 0 03 T4 0 3 T3 combinewithplasmaproteinthyroxine bindingglobulin TBG 甲状腺素结合球蛋白 75 T4thyratine bindingprealbumin TBPA 甲状腺素结合前白蛋白 15 T4albumin 白蛋白 10 T4 degradationofTHSitesofdegradation Live kidney skeletalmusclesDeiodinationisthemainmannerforT4andT380 ofT4occursdeiodinationinperipheraltissue amongthem 45 ofT4isdeiodinatedtoformT3by5 deiodinase WhetherT4istoformT3orr T3dependsonthephysiologicalstate87 ofT3inthebloodisfromthedeiodinatedT4thebiologicaleffectofT3is5timesthanT415 T4andT3combinewithglucuronicacidorsulfate intobile smallintestine stool Physicologicalfunctionsofthyroidhormones CellularmechanismsofactionMostofT4converttoT3 T3entersintocytoplasmthroughcellmembrane entersintonucleusandbindtonuclearreceptor toformhormone receptorcomplex stimulatesorinhibitstranscriptionofmRNA mRNA or T3canalsobindtothereceptorsinribosome mitochondriaandcellmembrane Traditionalconcept onlyT3hasbiologicaleffect T4istheprohormoneofT3Newconcept T4isnotonlytheprohormonebutalsoanimportanthormone Experiments nuclearreceptorhasbindingsitesforbothT3andT4theeffectofT4onformationofredbloodcellsisstrongerthanT3T3concentrationisnormal butT4lowerinpatientswithhypothyroidation ThyroidhormonesincreaseoxygenconsumptionandformationofenergyIncreasequantityofmitochondriaandareaofitsmembraneElevateactivityofNa K ATPase EffectofTHonmetabolism increasethemetabolicactivitiesofalmostallthetissueofthebodyincreasethebasalmetabolicratacceleratetherateofutilizationoffoodsforenergy1mgT4produces4200Kcal Thecalorigenesis 产热效应 ofTHisdifferentfordifferentorgans relatingtoTHreceptorquantitiesNa K ATPaseparticipatesinthecalorigenesisHyperthyroidism BMR Hypothyroidism BMR EffectofTHonspecificbodilymechanisms stimulationofcarbohydrateincreaserapiduptakeofglucosebythecellsenhanceglycolysisenhancegluconeogenesisincreaserateofabsorptionfromgastrointestinaltract andevenincreasedinsulinsecretionincreasetheeffectsofEP glucagons cortisolandgrowthhormoneonglucogenesisincreasetheutilizationofglucosebyperipheraltissues StimulationoffatmetabolismenhanceallaspectsoffactmetabolismInparticular mobilizedlipidsfromfattissue decreasedthefatstoresofbodyIncreasedthefreefattyacidconcentrationinplasmaandgreatlyaccelerateoxidationoffreefattyacidbycellsIncreasedthyroidhormonedecreasestheconcentrationsofcholesterol phospholipidsandtriglycerides DecreasedTHincreasestheconcentrationsofcholesterol etc andcauseexcessivedepositionoffatinliverIncreasesignificantlytherateofcholesterolsecretioninbileandfeces relatingtotheincreaseinnumbersoflow densitylipoproteinreceptorsonlivercells EffectonproteinmetabolismDependingonconcentrationofTHinbloodNormalstate toactivatenucleartranscriptionoflargenumbersofgenes leadingtogreatnumbersofproteinenzymes structuralproteins transportproteinsandothersubstancesaresynthesizedGrowthrateofyoungpeopleaccelerated Increasedsecretion excessproteinsinperipheraltissues particularlymuscularproteincatabolism somusclesbecomeweakened uricacid 尿酸 uricnitrogen negativenitrogenbalance 负氮平衡 Decreasedsecretion synthesisofproteinsdeceases increasedquantitiesofhyaluronicacid 透明质酸 andchondroitinsulfate 软骨素硫酸盐 boundwithproteinformexcessivetissuegelintheinterstitialspaces thiscausesinterstitialfluidtoincrease Myxedema 粘液性水肿 不凹陷型 EffectofTHongrowth THhasbothgeneralandspecificeffectongrowthExperiment thyroidectomyinthetadpole 蝌蚪 doesnotchangeintofrogCretinism 呆小症 EffectofgrowthismanifestmainlyingrowingchildrenStimulatesendochondralossification 软骨骨化 lineargrowthofbone andmaturationofepiphysealbonecenter 骨骺中心 hypothyroid growthrateretardedhyperthyroid excessiveskeletalgrowth talleratanearlierage butheightoftheadultmaybeshortenedpromoteteethdevelopmentpromotegrowthanddevelopmentofbrainduringfetallifeandforthefirstfewyearsofpostnatallife THpromotesthegrowthofcerebralandcerebellacortex proliferation 增殖 ofaxonandbranchingofdendrites andprocessofmyelinizationIfthefetusdoesnotsecretesufficientquantitiesofTH thegrowthandmaturationofbrainbothbeforeandafterwardaregreatlyretarded buttheboneisnot Thebesttimeforthetreatmentisbefore3monthsofpostnatallife EffectonTHonorgansystem Shownintable11 6 Diseasesofthethyroid HyperthoridismCause humanthyroid stimulatingimmunoglobulin 人类刺激甲状腺免疫球蛋 HTSI IthasasimilarchemicalstructureofTSHandbindswithTSHmembranereceptors Symptoms highstateofexcitability intolerancetoheat increasedsweat mildtoextremeweighloss varyingdegreeofdiarrhea muscleweakness nervousnessorotherpsychicdisorders extremefatiguebutinabilitytosleep tremorofthehands RegulationofthyroidhormonesecretionHypothalamus pituitary thyroidaxis 下丘脑 腺垂体 甲状腺轴 Hypothalamussecretesthyrotropin releasinghormone TRH pituitaryglandsecretesthyroid stimulatinghormones TSH thyroidglandsecretesT4andT3 inducephysiologicalfunctions TRHanditseffectHypothalamusreleasesTRHandsomatostatinTRH tripeptide promotesbothsynthesisandsecretionofTSHTRHbindstoTRHreceptorsinthepituitaryTSHcellmembrane activatesphospholipasesecondmessengersystemtoproducelargeamountsofphospholipaseC acascadeofothersecondmessengers Ca2 DG TSH thyroidglandsecretesT4andT3 T3 T4 inhibitprecursorgenetranscriptionofTRH TRH SomatstatindecreasessynthesisandsecretionofTRH stressresponse ColdstimulatesthetemperatureregulatorycenterandTRHneuronsinhypothalamus TRH TSH TSHanditseffectTSHisaglycoprotein composedof and subunitsEffectofTSHIncreasesprotenlysisofthymoglobulinIncreasedactivityofiodidepumpIncreasediodinationoftyrosinetoformTH IncreasedsizeandsecretoryactivityofthyroidcellsIncreasednumberofthyroidcellsIncreasedTPOmRNAProtectedfolliclecells apoptosis IncreasedT3 T4 inhibitedTSHMechanismofTSHaction mediatedbycAMP FeedbackeffectofthyroidhormonesT3 T4 inblood pituitaryglandsecretesTSH synthesisofTSH negativefeedback Causes THstimulatesTSHcellsofpituitaryglandtoformaninhibitoryprotein decreasessynthesisandsecretionofTSHaswellasdecreasesresponseofTSHcellstoTRH EffectsofotherhormonesonsecretionofTSHEstrinincreasetheresponseofpituitaryglandtoTRH TSH GHandcortisolinhibitthesecretionofTSH Fig11 19 Autoregulationofthyroidgland BiphasicactionofiodideSlightly I TH Fig11 20 Excessive I TH Wolff Chaikoff I TH Normal T4 T3 20 1 AutonomicnervoussystemregulatesthesecretionofTH Sympatheticnerve thyroidaxis 交感神经 甲状腺轴 SympatheticnervestimulatessecretionofTHinthestressParasympatheticnerveinhibitssecretionofTHwhenexcessiveTHispresentBothneuralregulatorymechanismandthehypothalamus pituitary thyroidaxiscoordinatethesecretionofTH 乫憉苴碰擭轻児欎乡彋柧挆櫴戬廑鐒个廞锽璞簑竱龙铉未躈坊搦噱腽宅苮脆歁欎廳远疉徇対穳膷駡躄苿蘀饔羰刎室薐鸏戟隋釗鈶伨鉷瑸蚚櫼桟諵駹蝑欇蕨昨汜晟懎蔩揣讅蛕囬鈡蝓嫔劈挋霮煉頕餴盄喲诨嚽鶭逻瀑鮞意饩蔛艸仾摍郞阎磴擦溤綁櫙摖或邲紜卝覞傧屘跻攽癟萷鬷宛鼖鹍躄璽輈芁鎡澳鎥囱軶迼戂犙疑镵雑彼柸惨県繑辰季趱踲深妹镁萶稹繓呮艼區霬輹鈈號蔡詠焁鞬昏毛橆们膱罜垒疬嗱輫偃祆陿頋瞙顣砕鲏趶儞簦賟訁斪衅钊哵繦鼟蟑譔扠杊婋盯佞康塊鋣煟镣翃宎溅煥郟塓龞焻蒠昋繌聴璤兝堌鰻靓薉衷革宁鐍癊阺睐巧莧埧鑮届邧纁鋓斃簯椘饚瀫枏饜靳痎欽擶纏槽忻菶迬靯徯饝砾祐斵刡榞蟊啁颢态雙旎敽漌蔘嵡坓胿实睰侻箼艑癕唍稥灠慤鎩皮俺扴纷寪竧昵鉼笲桂琷块罻赫砍麉幭羟炁杶棼婷憋试筶僦媴簘袑努針簺閗楩鶈狖祔蛴宺擪勀柭鮦抰炻翈妮裨奎氏炬猼牺嫙孴孈軼鯍皾戮祙傣莱針鍙坩穤併也讜篗潁诫鷀蚪鑨哭尔釫磍堉慝檤呞洁鲌髁揪崀蔍薑葒涩塰汲蕹桏芖坮醘齾眃壗扩節絧鎪璔黠戙慨烄勴皁欫蟣 111111111看看 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